Learning from –omics strategies applied to uncover Haemophilus influenzae host-pathogen interactions: Current status and perspectives

Abstract

Haemophilus influenzae has contributed to key bacterial genome sequencing hallmarks, as being not only the first bacterium to be genome-sequenced, but also starring the first genome-wide analysis of chromosomes directly transformed with DNA from a divergent genotype, and pioneering Tn-seq methodologies. Over the years, the phenomenal and constantly evolving development of –omic technologies applied to a whole range of biological questions of clinical relevance in the H. influenzae -host interplay, has greatly moved forward our understanding of this human-adapted pathogen, responsible for multiple acute and chronic infections of the respiratory tract. In this way, essential genes, virulence factors, pathoadaptive traits, and multi-layer gene expression regulatory networks with both genomic and epigenomic complexity levels are being elucidated. Likewise, the unstoppable increasing whole genome sequencing information underpinning H. influenzae great genomic plasticity, mainly when referring to non-capsulated strains, poses major challenges to understand the genomic basis of clinically relevant phenotypes and even more, to clearly highlight potential targets of clinical interest for diagnostic, therapeutic or vaccine development. We review here how genomic, transcriptomic, proteomic and metabolomic-based approaches are great contributors to our current understanding of the interactions between H. influenzae and the human airways, and point possible strategies to maximize their usefulness in the context of biomedical research and clinical needs on this human-adapted bacterial pathogen.

Immunoinformatics design of multi-epitope peptide-based vaccine against Haemophilus influenzae strain using cell division protein

“…The Hi genome (Rd KW20) was sequenced first among the members of Pasteurellaceae family (Pinto et al 2019 ). The genome size is 1,830,137 base pair with 38% GC content (López-López et al 2021 ).…”

“…Hi adheres to host cells and exhibits pathogenicity via various modes of transmission (Chen et al 2018 ). One of the crucial steps in infection and pathogenesis is the initial adhesion of Hi to the host cells (López-López et al 2021 ). Hi adheres to host cells and exhibits pathogenicity such as the capsule, the adhesion proteins, the IgA1 protease, and, last but not least, the lipooligosaccharide (Huska et al 2022 ; Vitovski et al 2002 ; Kilian et al 1983 ).…”

Interrogation of Essentiality in the Reconstructed Haemophilus influenzae Metabolic Network Identifies Lipid Metabolism Antimicrobial Targets: Preclinical Evaluation of a FabH β-Ketoacyl-ACP Synthase Inhibitor

“…Our metabolic model and FabH RdKW20 :FabHi complex structure relied on the H. influenzae RdKW20 genome content and FabH RdKW20 crystal structure ( 42 , 43 ), respectively. However, H. influenzae strains show high genomic and phenotypic diversity ( 3 , 44 ). To anticipate the potential role of FabHi as a broad inhibitor of H. influenzae , we examined the sequence variability of the fabH locus across a well-characterized genome-sequenced set of strains collected from COPD sputum samples over time, grouped in clonal types (CTs) ( 45 , 46 ).…”

Beyond the List: Bioagent-Agnostic Signatures Could Enable a More Flexible and Resilient Biodefense Posture Than an Approach Based on Priority Agent Lists Alone

“…Host-pathogen studies generally revolve around individual host-pathogen interactions (e.g., Bacillus anthracis infection in humans); however, commonalities exist in host responses to disparate pathogens, which could serve to nucleate the development of BASs (Figure 1). Adding to an already large body of knowledge on host-pathogen interactions [9][10][11], 'omics approaches are beginning to illuminate the ways that host and pathogen pathways work in concert to give rise to disease phenotypes [12][13][14]. Below, we briefly describe three broad types of host responses that scientists could measure and incorporate into BASs to enable response pattern recognition and biosurveillance; we also suggest further study of host-pathogen interactomes as a way of identifying complex, multi-omic BASs.…”